Major adverse cardiovascular events (MACE, or major adverse cardiac events) is a composite endpoint frequently used in cardiovascular research.^[1][2] Despite widespread use of the term in clinical trials, the definitions of MACE can differ, which makes comparison of similar studies difficult.^[3]

The so-called "classical 3-point MACE" is defined as a composite of nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death.^[4][5] But another study defines MACE as "CVD events, admission for HF (Heart Failure), ischemic cardiovascular [CV] events, cardiac death, or MACE".^[6] Yet another study defined MACE as "CV death, hospitalization for HF, or myocardial infarction (MI)".^[7]

The heterogeneity of the sets defining MACE, hampering systematic reviews and meta-analyses, has been repeatedly criticized.^[8][9][10]

Which conditions are risk factors for MACE depends on some characteristics of the investigated cohort. Established risk indicators in the general population include age, pre-existing cardiovascular disease, smoking, diabetes mellitus, elevated concentrations of triglycerides and non-HDL cholesterol concentration, reduced HDL concentration and hypertension, as, e. g., demonstrated by the Framingham Heart Study. More recently, additional risk indicators have been identified, e. g. type 2 allostatic load,^[11] high-sensitivity C-reactive protein, d-dimer level,^[12] renal failure^[13] and altered thyroid function.^{[14][15][16][17]}

Two reviews have concluded that SGLT2 inhibitors benefit patients with atherosclerotic MACE.^[18][19] One of those studies defined MACE as the composite of myocardial infarction, stroke, or cardiovascular death.^[18] Other studies have shown MACE to be potently predicted by levels of ceramide found in patients.^[20]